Key Points
- To investigate the mechanisms underlying the loss of vascular insensitivity to angiotensin II in pregnancy-induced hypertension by evaluating AT1R and AT2R receptor expression in endothelial and smooth muscle cells.
- Incubated human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) for 0 to 12 hours with serum from women with normal pregnancy or pregnancy-induced hypertension (PIH).
- Semiquantified AT1R and AT2R mRNA expression relative to GAPDH using multiplex RT-PCR, and evaluated AT1R protein expression via immunocytochemistry with and without anti-TNF-alpha antibody or valsartan.
- PIH serum significantly increased HUVEC AT1R mRNA to 1.48 +/- 0.44 compared to 0.25 +/- 0.14 with normal pregnancy serum after 12 hours, while decreasing AT2R mRNA to 0.14 +/- 0.02 compared to 0.31 +/- 0.08.
- Anti-TNF-alpha antibody (20 microg/mL) significantly reduced both the elevated AT1R-to-AT2R mRNA ratio and endothelial AT1R protein expression induced by PIH serum.
- Valsartan (1 to 10 nmol/L) significantly increased AT2R mRNA in HUVEC, whereas VSMC AT1R mRNA increased with serum from both normal pregnancy and PIH cohorts.
Structured PICO
PPopulationHuman umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) incubated with serum from normal pregnant women and pregnancy-induced hypertension (PIH) patients
IInterventionIncubation with serum from PIH patients for 0 to 12 h (with or without anti-TNF-alpha antibody or valsartan)
CComparatorIncubation with serum from normal pregnant women
OOutcomeAT1R and AT2R mRNA expression (ratio to GAPDH mRNA) and AT1R protein expressionsurrogate
In pregnancy-induced hypertension, endothelial AT1R expression is increased and AT2R expression is decreased, a process potentially mediated by TNF-alpha.